One of the long existing primary goals of medicine is the relief of pain. Relief is sought most generally by the administration of analgesic drugs which produce a state of decreased awareness of the sensation and increase of the pain threshold.
Almost all potent analgesics evoke reactions other than the relief of pain. Some of the reactions are gastrointestinal disturbances, nausea, constipation and vomiting. Among the more serious of the side reactions and one frequently found in analgesic drugs is respiratory depression. Thus, in the use of anlagesics in man, considerations other than the primary effect (analgesia), must be made and drugs for pain relief are sought which have maximum analgesic effect accompanied by minimum side reactions. It is difficult to satisfy these requirements with a single chemical entity since generally a potent analgesic has accompanying serious side reactions while a drug with little or no side effects is generally less effective as an analgesic.
Thus, there is a continuing search for a combination of two or more drugs whereby the total quantity of drug can be reduced and which can be employed in such proportions as to produce maximum analgesic effect with little or no side effects. When one or both of the components of a combination is known to possess pain-relieving properties, but these properties are increased many fold over that which would be expected by simple addition of these properties, the net effect of the combination is commonly referred to as "potentiation".
It has now been found that the analgesic effect of zomepirac is potentiated by butorphanol.
Zomepirac is the generic name for 5-(4-chlorobenzoyl)-1,4-dimethyl-1H-pyrrole-2-acetic acid represented by the formula; ##STR1## Zomepirac is useful as an analgesic agent either in its acid form or as a pharmaceutically acceptable salt thereof. The pharmaceutically acceptable salts are those obtained from appropriate organic or inorganic bases. Preferred salts include the sodium and potassium salts. Zomepirac is commercially available in the form of a salt thereof as zomepirac sodium, which is the generic name for sodium 5-(4-chlorobenzoyl)-1,4-dimethyl-1H-pyrrole-2-acetate dihydrate.
Butorphanol is the generic name for 17-(cyclobutylmethyl)morphinan-3,14-diol or levo-N-cyclobutylmethyl-3,14-dihydroxymorphinan. It can be used as such or in the form of a pharmaceutically acceptable salt, preferably of a weak organic acid such as tartaric acid.
Butorphanol is recognized as an analgesic agent with useful antinociceptive properties. However, in certain instances it may produce sedation, psychotomimatic and dysphoric effects. The effect of the combination of these drugs on the analgesic properties was not known prior to our work.